Synthesis and SAR studies of trisubstituted purinones as potent and selective adenosine A2A receptor antagonists.

作者信息

Shao Yuefei, Cole Andrew G, Brescia Marc-Raleigh, Qin Lan-Ying, Duo Jingqi, Stauffer Tara M, Rokosz Laura L, McGuinness Brian F, Henderson Ian

机构信息

Pharmacopeia, Inc., PO Box 5350, Princeton, NJ 08543, USA.

出版信息

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1399-402. doi: 10.1016/j.bmcl.2009.01.042. Epub 2009 Jan 19.

DOI:10.1016/j.bmcl.2009.01.042

PMID:19181527

Abstract

A series of trisubstituted purinones was synthesized and evaluated as A(2A) receptor antagonists. The A(2A) structure-activity relationships at the three substituted positions were studied and selectivity against the A(1) receptor was investigated. One antagonist 12o exhibits a K(i) of 9nM in an A(2A) binding assay, a K(b) of 18nM in an A(2A) cAMP functional assay, and is 220-fold selective over the A(1) receptor.

摘要

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